For many years, attempts have been made to provide drug delivery technologies which are patient-friendly, non-invasive, and economically viable alternatives to injecting large macromolecule proteins. Some of the earliest efforts involved transdermal delivery via electroporations but this has mostly been abandoned because of technical difficulties in providing systems to carry large molecules through the skin. Oral delivery, which would clearly be the preferable dosage form, has had some success. However, a major obstacle is the degradation and denaturization of proteins in the gastrointestinal tract. The likelihood of the right amount of drug actually getting into the bloodstream reproducibly seems difficult even with the most advanced carrier technology. The lung appears advantageous because of the enormous surface area of the alveoli, and the fact that the lung can absorb both small and large molecules while simultaneously filtering out microparticle carriers and other unwanted toxins in the air. Large proteins, including antibodies, are readily absorbed through the alveoli either directly into the circulatory system or, more frequently, via the lymphatic system, which subsequently releases the drug into the bloodstream. Proteins in excess of 50 kilodaltons in molecular weight, which include the overwhelming majority of all biotech products on the market and in development, have been successfully delivered via the lung. No other non-invasive drug delivery system seems to have the potential to deliver large molecules as efficiently and quickly as pulmonary delivery through the lung.
Conventional metered dose inhalers, primarily used for asthma, deliver drugs into the upper branches of the lung. The ability to deliver drugs via small molecules through the deep lung and into the alveoli was one of the most significant technical breakthroughs in drug delivery. Conventional metered-dose inhalers (MDIs) deliver between 0-80% of the drug depending on the formulation and the propellant drug ratio.
In the current U.S. market for many drugs, improvements in drug delivery technology could have a significant impact. Rapid onset of action via non-injectable methods is an enormous opportunity. Pain management situations, e.g. breakthrough pain, post-surgical, migraine, and trauma/emergency room, represent a huge opportunity. New products are needed to address these drug delivery needs, while simultaneously providing patients with a convenient user friendly mechanism and physicians with a tool to improve overall diseases by improving therapy, compliance, and to prevent or reduce expensive hospital stays.
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